Open trials

Clinical research is an essential work to improve the treatment of oncological patients. This work is fruitless if it is carried out without cooperation projects between several hospitals. The cooperative effort is especially important in handling sarcomas, not only because of their rarity, but also due to their biological heterogeneity and the variability of their clinical behavior.

Inclusion Criteria

Subjects must provide written informed consent prior to performance of studyspecific procedures or assessments and must be willing to comply with treatment and follow-up. Informed consent may be obtained prior to start of the specified screening window. Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study such as bone scan) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol

Measurable disease criteria: At least one measurable lesion. All the cases will be evaluated with RECIST criteria and CHOI criteria (Hansfield Units must be provided)

Protocol will be built in English. For Inform Consent language will be adapted for every different country

Paraffin embedded tumors must be provided for centralized pathology review. Additionally, serum sample will be collected (3 for each patient) to analyze angiogenic serum biomarkers. If pharmacodynamic studies would be considered, a pre and post treatment biopsy should be performed in order to collect frozen and paraffin embedded tumor tissue

Adequate organ system function

Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in Pregnancy Section in overall Safety Section during the study and for [x hours or days - based on half-life of compound] following the last dose of investigational product

Exclusion criteria

Prior malignancy. Subjects who have had another malignancy and have been disease-free for 10 years, or subjects with a history of completely resected nonmelanomatous skin carcinoma or successfully treated in situ carcinoma are eligible

Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids orenzyme-inducing anticonvulsants in prior X time interval

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding, inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel

History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class II, III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (see Section YYY Appendix Y for description)

Poorly controlled hypertension [defined as systolic blood pressure (SBP) of 140 mmHg or diastolic blood pressure (DBP) of 90mmHg]. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be <140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in order for a subject to be eligible for the study (see Section XXX for details on BP control and re-assessment prior to study enrollment)

History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible

Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery)

Evidence of active bleeding or bleeding diathesis

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed

Recent hemoptysis (³½ teaspoon of red blood within 8 weeks before first dose of study drug)

Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures

Unable or unwilling to discontinue use of prohibited medications listed in Appendix C Section XX for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study (Appendix C) (Section XX)

Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazoapnib or chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment

Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia

Recruitment status

TRASTS study: Prospective, multicentric clinical Trial Phase I-II, exploring the combination of trabectedin and radiotherapy on soft tissues sarcomas, is open to patient recruiting. right now there is a free slot on Phase I Cohort A dose 1,5 mg/m2, required to be included in order to close Phase I of the trial. Cohort B, after closing Phase I, is open to recruiting on Phase II dose 1,5 mg/m2. Given the importance of the trial, we encourage you to keep adding patients

Inclusion criteria Cohort A

The patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.

Aged between 18 and 70.

Patients must have a diagnostic of Soft Tissue Sarcoma with metastasis limited to lung, and not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy. A central review will be performed therefore patient should have an available tumor sample shipped before enrolment.

Patients must have documentation of disease progression within 6 months prior to study entry.

The patient must have been considered eligible for systemic chemotherapy. A maximum of two previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included.

Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry.

Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.

Disease distribution in lungs allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point. All lung nodules should be irradiated, otherwise patient is not eligible.

It should be performed HBV and HCV serologies prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. If a potential patient is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the patient should NOT be included in the study (if a qualitative PCR cannot be performed then patient will not be able to enter the study)

Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry.

Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.

It should be performed HBV and HCV serologies prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA HBV+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. If a potential patient is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the patient should NOT be included in the study (if a qualitative PCR cannot be performed then patient will not be able to enter the study).

Recruitment status

Observational, retrospective and multicentric study to evaluate second line treatments in patients with soft tissue sarcomas, locally advanced or metastatic, progressing to anthracyclines and/or ifosfamide. Currently the trial is on a period of tissue sample analysis. The patient recruiment period has been extended to those that have been treated up to March 2017 to reach a goal of a n=300. On December, 6 new patients were included. Up to date there is a total of 262 registered patients.

Inclusion criteria

1. Patients must provide written informed consent prior to performance of studyspecific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient’s routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.

11. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to enrollment and agree to use birth control measures during study treatment and for 7 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method.

11. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Females of child-bearing potential and males and must agree to use highly effective contraceptive precautions during the trial and up to 6 months following the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (that is, <1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner.

Exceptions: Females not of child-bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause. A “postmenopausal woman” is a woman meeting either of the following criteria:

spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example, oral contraceptives, hormones, gonadotropin releasing hormone, antiestrogens, selective estrogen receptor modulators (SERMs), or chemotherapy

Inclusion criteria

1. Patients must provide written informed consent prior to performance of studyspecific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient’s routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.

11. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to enrollment and agree to use birth control measures during study treatment and for 7 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method.

Inclusion criteria

Histologically confirmed ES.

Disease recurrence or progression after completion of first line treatment. OR Refractory disease, defined by progression during first line treatment or within 12 weeks of its completion. Disease progression will be based on RECIST criteria (see Appendix 1). The appearance of new bone lesions on bone scan will require confirmation with cross-sectional imaging.

Soft tissue disease component evaluable by cross-sectional imaging (RECIST). Patients with bone disease without a measurable soft tissue component or bone marrow disease only will be eligible for the study but will not contribute to the phase II primary outcome measure.

Inclusion criteria Cohort 1: Desmoid tumor

1. Subjects must voluntarily sign the informed consent form before any study test is conducted that is not part of routine subject care.

2. Subjects with pathologic diagnosis of deep desmoid tumor of extremities, trunk wall or head and neck region.

3. Subjects must be symptomatic due to tumor desmoid mass.

4. Age: 18-80 years (both ages included).

5. Subjects could have received 1 previous chemotherapy line if the scheme was methrotrexate and vinca alkaloids. Importantly, if this is the case, it must be documented that symptoms have gotten worse or simptoms are stable in the context of disease progression (RECIST 1.1).

12. Men or women of childbearing potential must use an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study treatment. Women of childbearing potential must have a negative urine or serum pregnancy test before study entry.

13. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+) remaining at investigators' discretion the preventive treatment with lamivudine. If a potential subject is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the subject should NOT be included in the study (if a qualitative PCR cannot be performed then subject will not be able to enter the study).

Exclusion criteria Cohort 1: Desmoid tumor

2. Subjects with desmoid tumor of abdominal cavity (abdominal wall is not an exclusion criteria)

3. Desmoid tumor with ill-defined margins.

4. Unavailability to undergo MRI.

5. Previously irradiated target lesion.

6. Pre-existing neuropathy greater than grade 1.

7. Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years. However, localized squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ of the cervix or other malignancies requiring only locally ablative therapy, will not result in exclusion.

11. Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study.

12. Known hypersensitivity to protein bound paclitaxel

13. Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol

12. Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative urine pregnancy test before study entry.

13. HBV and HCV serologies must be performed prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+ ,DNA VHB+) remaining at investigators' discretion the preventive treatment with lamivudine. If a potential subject is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the subject should NOT be included in the study (if a qualitative PCR cannot be performed then subject will not be able to enter the study).

Exclusion criteria Cohort 2: DSRCT and ES

1. Less than 4 weeks elapsed since prior exposure to chemotherapy.

2. Pre-existing neuropathy greater than Grade 1.

3. Other active invasive malignancy requiring ongoing therapy or expected to require systemic therapy within two years. However, localized squamous cell carcinoma of the skin, basal cell carcinoma of the skin, carcinoma in situ of the cervix or other malignancies requiring only locally ablative therapy, will not result in exclusion.

7. Pregnant women are excluded due to the potential for teratogenic or abortifacient effects of nab paclitaxel because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued prior to participation of the mother on study.

8. Known hypersensitivity to protein bound paclitaxel.

9. Any other concurrent condition that in the investigators opinion would jeopardize compliance with the protocol.

Exclusion criteria

Participating Centers

Recruitment status

Phase II, single arm, non-randomized and multicenter clinical trial of regorafenib as a single agent in the first-line setting for patients with metastatic and/or unresectable KIT/PDGFR Wild Type GIST. This regorafenib trial in patients with GIST is active and open to recruit the first patients. From GEIS we ask you that before starting a Imatinib treatment with advanced GIST, a mutational analysis is made on the center, and if the result is GIST Wild Type the patient might be sent to one of the mentioned centers to be included on this trial and treated with regorafenib for free. For further information you can contact the CDC.

Inclusion criteria

Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up. Informed Consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient´s routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.

Screening of mutations done in exon 11, 9, 13 and 17 in KIT gene and in 12 and 18 exons of PDGFR gene

Subjects must have at least one measurable lesion according to RECIST v1.1 criteria. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrolment.

International Normalized Ratio (INR) ≤1.5xUNL and partial thromboplastin time (PTT) or activated partial thromboplastine time (aPTT) ≤1.5xUNL. Subjects who are being treated with an anti-coagulant, such as warfarin or heparin, will be allowed to participate provided that no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a predose measurement as defined by the local standards of care.

Women of childbearing potential and men must agree to use adequate contraception from the moment of signing the Informed Consent Form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.

Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment.

Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the start of study medication.

Congestive Heart Failure New York Heart Association (NYHA) ≥ class 2.

Unstable angina (angina symptoms at rest, new-onset angina, ie, within the last 3 months prior to entering study) or myocardial infarction (MI) within the past 6 months before the start of study medication.

Inclusion criteria

To be eligible for inclusion in the study, each patient must fulfil each of the criteria below.

Age >18.

Morphological and immunohistochemical documentation of GIST (immunostaining for KIT/(CD117) and/or DOG-1 (anocatamin-1)) must be positive on a tumour sample. Patients with demonstrated mutation in KIT or PDGFRA may be entered to the study despite negative immunostaining for KIT and DOG-1 provided that tumour histology is compatible with GIST. Tumour tissue must be available for central pathology review.

Mutation analysis of KIT and PDGFR genes has been carried out (sequencing of at least KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 is recommended before a tumour can be considered wild type).

High risk of tumour recurrence following surgery and 3 years of adjuvant imatinib defined as one of the following:

gastric GIST with a mitotic count >10/50 HPFs (HPF, high power field of the microscope),

non-gastric GIST with a mitotic count >5/50 HPFs, or

tumour rupture

Tumour rupture may have occurred before or at surgery. Tumour rupture is defined by spillage of the tumour contents into the abdominal cavity. A core needle biopsy from the tumour, or tumour bleed with no apparent spillage of the tumour contents, are not considered ruptures.

Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2.

Adequate organ function. All of the following criteria must be filled: total bilirubin

Female patients of childbearing potential must have a negative pregnancy test within 14 days before initiation of study drug dosing. Postmenopausal women must have amenorrhea for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. For female, a highly effective method for birth control must be used, which means that the method can achieve a failure rate of less than 1% per year when used consistently and correctly. All females of child-bearing potential must be informed of such methods, and must also, if sexually active, accept a monthly pregnancy test if randomised to prolonged imatinib use.

Patient willing to be followed up at the study site regardless of the result of randomisation.

Administration of adjuvant imatinib longer than for 3 years is planned regardless of the result of randomisation, or “life long” imatinib administration is planned.

Prior adjuvant (+ neoadjuvant) therapy with imatinib mesylate for at least 35 months has not been completed, or the total duration of prior adjuvant imatinib (+ neoadjuvant) exceeds the total of 37 months.

Neoadjuvant imatinib for a duration that exceeds 9 months.

A longer than 4-week break during adjuvant imatinib administration.

The dose of adjuvant imatinib at the time of completion of 3 years of adjuvant imatinib was 200 mg per day or less or greater than 800 mg per day.

Patient has received any investigational anti-cancer agents during adjuvant imatinib or between completion of adjuvant imatinib and the date of randomisation.

Patient has been free of another malignancy for less than 5 years except if the other malignancy is not currently clinically significant not requiring active intervention, or if the other malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other recent malignant disease is not allowed.

Inclusion criteria

1. Histologically or cytologically-confirmed advanced or metastatic GIST with a D842V mutation in the PDGFRA gene as determined by central laboratory testing (1)

2. Measurable disease as per modified RECIST 1.1 (Appendix V) (1)

A lesion in an area that was previously treated with local therapy (e.g. radiation, surgery, or cryotherapy) can be considered measurable disease as long as there is objective evidence of progression of the lesion prior to randomization

8. Female subjects with reproductive potential must have negative serum or urine pregnancy test Female subjects who meet at least one of the following criteria are defined as women of non-reproductive potential:

Female subjects with reproductive potential in combination with their partner must use 2 forms of highly effective methods of contraception during study treatment and for at least 30 days after ending treatment

Male subjects in combination with their partner must use 2 forms of highly effective methods of contraception during study treatment and for at least 90 days after ending treatment

12. Written informed consent before any study-specific procedure is performed (5)

Rationale for Inclusion Criteria

These criteria are included to:

(1) Ensure enrollment of representative subjects for the planned indication

(2) Minimize potential risks to subject safety

(3) Prevent pregnancy during treatment

(4) Exclude potential confounding effects from the evaluation of the investigational drug

(5) Ensure the study will be conducted in compliance with Good Clinical Practice (GCP)

Malignancy treated with curative intent and with no evidence of disease and considered to be at low risk of recurrence by the treating physician

Adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease

Adequately treated cervical carcinoma in situ with no evidence of disease

Adequately treated breast ductal carcinoma in situ with no evidence of disease

Adequately treated prostatic intraepithelial neoplasia with no evidence of disease

Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ with no evidence of disease

4. Any disorder that compromises the subject’s ability to give written informed consent and/or to comply with study procedures (5)

5. Any severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator, may prevent the subject from completing the study, interfere with the evaluation of safety and/or efficacy, or interfere with the interpretation of the study results (4), (5)

General

6. Female subject who is pregnant or breastfeeding, or planning to become pregnant within 30 days after ending treatment (2)

Recruitment status

If you are interested in receiving the entire protocol of a specific trial on PDF format, just send an email to This email address is being protected from spambots. You need JavaScript enabled to view it. with your full name, workplace, your job position and the protocol you are interested in.

ABOUT GEIS

INFORMATION

This site contents are not a valid substitute for medical diagnosis, prognosis or treatment given by a doctor. GEIS must insist that the decisions related to sarcoma patients must always be sanctioned by a specialist familiar to this condition after personally meeting the subject. This website operates under its User Terms and Conditions.